Reaction #51227

Reaction equation

N-benzyloxycarbonyl-trans-4-[(5-hydroxylmethyl-2-isoindolinyl)carbonyl]cyclohexylamine

triethylamine

methanesulfonyl chloride

chloride

→

trans-4-[(5-morpholinomethyl-2-isoindolinyl)carbonyl]cyclohexylamine

Solvents

Water

Conditions

Workup

1. 1
   Temperaturecooling
2. 2
   Temperaturecooling for 1 hour
3. 3
   Extractionthe mixture was extracted with ethyl acetate
4. 4
   DryingAfter the extract was dried over sodium sulfate
5. 5
   Otherthe solvent was removed under reduced pressure
6. 6
   workup.ADDITIONTo the residue were added 5 ml of dimethylformamide and 0.25 ml of morpholine
7. 7
   workup.STIRRINGthe mixture was stirred at room temperature overnight
8. 8
   workup.ADDITIONWater was added to the reaction mixture
9. 9
   Extractionthe mixture was extracted with ethyl acetate
10. 10
    DryingAfter the extract was dried over anhydrous sodium sulfate
11. 11
    Otherthe solvent was removed under reduced pressure
12. 12
    OtherThe residue was purified by silica gel chromatography (solvent: chloroform-methanol=100:1)
13. 13
    workup.ADDITIONThis compound was treated with palladium-carbon under hydrogen atmosphere

Procedure

0.15 ml of triethylamine and 0.07 ml of methanesulfonyl chloride were added to 10 ml of a tetrahydrofuranmethylene chloride suspension containing 0.31 g of N-benzyloxycarbonyl-trans-4-[(5-hydroxylmethyl-2-isoindolinyl)carbonyl]cyclohexylamine under ice-cooling, and the mixture was stirred under ice-cooling for 1 hour. Water was added to the reaction mixture and the mixture was extracted with ethyl acetate. After the extract was dried over sodium sulfate, the solvent was removed under reduced pressure. To the residue were added 5 ml of dimethylformamide and 0.25 ml of morpholine, and the mixture was stirred at room temperature overnight. Water was added to the reaction mixture and the mixture was extracted with ethyl acetate. After the extract was dried over anhydrous sodium sulfate, the solvent was removed under reduced pressure. The residue was purified by silica gel chromatography (solvent: chloroform-methanol=100:1). This compound was treated with palladium-carbon under hydrogen atmosphere to obtain trans-4-[(5-morpholinomethyl-2-isoindolinyl)carbonyl]cyclohexylamine (Reference Example 13-24 in Table 8).

Source